A case report of recurrent C3 glomerulonephritis 18 months after renal transplantation
© The Author(s) 2016
Received: 7 October 2015
Accepted: 13 May 2016
Published: 15 August 2016
The recurrence of glomerulonephritis (GN) is critical to the prognosis of long-term renal transplant graft survival. C3 GN is a rare GN with a poor prognosis, and there are only a few reports of recurrent cases after renal transplantation. We recently experienced a case highly suspected of C3 GN recurrence.
The patient was a 67-year-old male who had suffered from end-stage renal disease (ESRD) and started dialysis at the age of 60. His primary renal disease was unknown. At the age of 63, renal transplantation was successfully performed. His serum creatinine (Cr) level was maintained at 1.2 to 1.5 mg/dl, with no urinary protein or occult blood until 18 months after the transplant when urinary occult blood and protein became constant, along with an elevated Cr level at 1.5 to 1.6 mg/dl. The tentative diagnosis following a protocol biopsy at 36 months was dense-deposit disease. However, the pathological findings of an episode biopsy performed 1 year later, when his Cr level elevated to 2.0 mg/dl after varicella zoster virus reactivation, revealed no acute rejection but were compatible with C3 GN.
These findings are consistent with a previous report on recurrent C3 GN that revealed relatively rapid loss of graft function, contrasting well with slow progression occurring in the native kidney. This case is possibly the first report in Japan of recurrent C3 GN after renal transplantation.
The recurrence of glomerulonephritis (GN) is a critical risk factor for long-term renal transplant graft survival. C3 GN is a rare GN with poor prognosis, and there are only a few reports of recurrent cases after renal transplantation. The following report details a case highly suspected of C3 GN that we recently experienced.
C3 glomerulopathy (C3GP) is a rare disease that is due to abnormalities in the alternative pathway (AP) suspected of being caused either by autoantibodies or genetic abnormalities in the AP pathway. C3GP includes dense-deposit disease (DDD) and C3 GN, both of which show glomerular deposition only for C3, but an absence of Ig deposition on IF. Sethi et al. reported EM findings with mesangial and/or subendothelial, intramembranous, and subepithelial depositions in C3 GN. The depositions were amorphous and appeared lighter and less sharply demarcated than immune-type electron-dense deposits . In our case, there was C3 staining at the mesangium and capillary and a lack of C1q, C4c, and Ig depositions on IF. An amorphous deposition was observed at the subendothelial and mesangial areas on EM at the third biopsy. Using these findings, we diagnosed C3 GN. Although C3 deposition was observed from the first biopsy, without any history of apparent infection, infection-related GN was incompatible.
Reports of recurrent C3 glomerulopathy after renal transplantation
Athanasiou Y et al (2011) 
One patient had a second transplant. Eight patients are well 1 to 23 years intact (Cr 0.9 mg/dl).
Servais et al (2007) 
Glomerulonephritis (GN) with isolated C3 deposits
No recurrence at 2 months after transplantation (C3NeF +). Recurrence at 1 month after transplantation with proteinuria and normal renal function (C3NeF −).
Olivia Boyer et al (2008) 
Atypical hemolytic and uremic syndrome associated with CFH deficiency
C3 deposition was positive at 5 years post-transplantation.
Kidney function is stable 9 years after transplantation.
Recurrence of GN with isolated C3 deposits 5 months later after kidney transplantation and TMA 4 years later. Six years later, kidney function was stable with regular plasma therapy.
Sethi et al (2012) 
Recurrence of C3 GN within 1 to 1.5 years of kidney transplantation. (One was C3NeF positive, another was C3 risk allele positive.)
Vernon KA et al (2011) 
Right after the transplantation, persistent microscopic hematuria was observed.
There is no established treatment for C3GP. For complement dysregulation in the pathogenesis of this disease, a supply of normal plasma has been suggested. Recently, a new therapy targeting an alternative complement pathway using the anti-C5 antibody [3–8] and soluble CR1  has been reported. However, controlled trials regarding the efficacy of these treatments have not yet been conducted. Reports on recurrent cases in grafts are very limited. To improve long-term graft survival, further investigation of treatment not only for the native kidney but also for the graft should be done.
In summary, compared to the native kidney, early recurrence and rapid loss of graft function was observed in our case. To better assess the indication of renal transplantation, further accumulation of such cases is required.
AP, alternative pathway; C3GP, C3 glomerulopathy; C3NeF, C3 nephritic factor; CFH, complement factor H; CFHR1-5, complement factor H-related 1-5; CHI, complement factor I; Cr, creatinine; DDD, dense-deposit disease; EM, electron microscopy; ESRD, end-stage renal disease; GN, glomerulonephritis; IF, immunofluorescence; Ig, immunogloblulin; LM, light microscopy; MMF, mycophenolate mofetil; MPGN, membranoproliferative glomerulonephritis; POY, post-operative year; PSL, prednisolone; TAC, tacrolimus; TMA, thrombotic microangiopathy; VZV, varicella zoster virus
HK, TM, TK, TT, EM took care of this patient and participated in decision of treatment. HK prepared the manuscript. EM revised it critically for important intellectual content. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Written informed consent was obtained from the patient.
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- Sethi S, Fervenza FC, Zhang Y, et al. C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int. 2012;82:465–73.View ArticlePubMedPubMed CentralGoogle Scholar
- Pratt JR, Basheer SA, Sacks SH. Local synthesis of complement component C3 regulates acute renal transplant rejection. Nat Med. 2002;8:582–7.View ArticlePubMedGoogle Scholar
- Zuber J, Fakhouri F, Roumenina LT, et al. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol. 2012;8:643–57.View ArticlePubMedGoogle Scholar
- Herlitz LC, Bomback AS, Markowitz GS, et al. Pathology after eculizumab in dense deposit disease and C3 GN. J Am Soc Nephrol. 2012;23:1229–37.View ArticlePubMedPubMed CentralGoogle Scholar
- Daiana E, Noris M, Remuzzi G. Eculizmab in a patient with dense deposit disease. N Engl J Med. 2012;366:1161–3.View ArticleGoogle Scholar
- Vivarelli M, Pasini A, Emma F. Eculizmab for the treatment of dense-deposit disease. N Engl J Med. 2012;366:1163–5.View ArticlePubMedGoogle Scholar
- Radhakrishnan S, Lunn A, Kirschfink M. Eculizmab and refractory membranoproliferative glomerulonephritis. N Engl J Med. 2012;366:1165–6.View ArticlePubMedGoogle Scholar
- McCaughan JA, O’Rourke DM, Courtney AE. Recurrent dense deposit disease after renal transplantation: an emerging role for complementary therapies. Am J Transplant. 2012;12:1046–51.View ArticlePubMedGoogle Scholar
- Athanasiou Y, Voskarides K, Gale DP, et al. Familial C3 glomerulopathy associated with CFHR5 mutations: clinical characteristics of 91 patients in 16 pedigrees. Clin J Am Soc Nephrol. 2011;6:1436–46.View ArticlePubMedPubMed CentralGoogle Scholar
- Servais A, Fremeaux-Bacchi V, Lequintrec M, et al. Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. J Med Genet. 2007;44:193–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Boyer O, Noel LH, Balzamo E, et al. Complement factor H deficiency and post-transplantation glomerulonephritis with isolated C3 deposits. Am J Kidney Dis. 2008;51:671–7.View ArticlePubMedGoogle Scholar
- Vernon KA, Gale DP, de Jorge EG, et al. Recurrence of complement factor H-related protein 5 nephropathy in a renal transplant. Am J Transplant. 2011;11:152–5.View ArticlePubMedPubMed CentralGoogle Scholar